Acute human diarrheal disease due to bacterial enterotoxins may be curtailed by antibacterial therapy and diminished by enhancement of active intestinal glucose absorption but, to date no effective pharmacologic control of fluid secretion has been achieved. Three problems related to the control of enterotoxin induced fluid secretion will be studied. (1) The kinetics, rate and duration of the secretory response to pure or highly purified preparations of cholera, Escherischia coli and Shigella enterotoxins, will be measured in an in vivo animal model. Utilizing I 125-cholera enterotoxin and simulataneous measurement of epithelial cell turnover with H3-thymidine, the secretory response will be correlated with evidence for alteration in cell turnover and persistent binding of toxin to the mucosa utilizing in in vitro techniques. (2) It is postulated that effective pharmacological inhibition of enterotoxin induced secretion can be best achieved with compounds which interact and bind preferentially to the intestinal mucosal cell surface membrane. The inhibitors to be studied will include: (a) Polypeptide Antibiotics, such as Polymyxin, which bind to phospholipid in cell membranes. In preliminary experiments, Polymyxin inhibited enterotoxin induced secretion by 80-90 percent; (b) Plant Lectins, such as Concanavalin A, which may alter binding affinity of enterotoxins for ganglioside and saccharide receptors at the cell surface, and (c) Plant Pectins, a group of polysaccharides widely utilized in therapeutics for treatment of acute diarrheal disease. (3) An increase in adenyl cyclase activity is a recognized response of intestinal epithelial cells to binding of cholera and Escherischia coli enterotoxin. Glycolipid and glycoprotein turnover in the plasma cell membrane may be changed when fluid secretion is induced by enterotoxins, and provide a similar "indicator" of mucosal cell secretory activity. Specific glycosyl transferase activity in brush border membrane, and in secreted fluid will be measured as an enzymatic indicator of secretory activity after cholera, Escherischia coli and Shigella enterotoxin exposure.